Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer

AIM:To investigate the feasibility of detecting aberrantly hypermethylated Wnt-antagonist gene promoters(SFRP2 and WIF-1)in fecal DNA as non-invasive biomarkers for early colorectal cancer(CRC).METHODS:The methylation-specific polymerase chain reaction assay was performed to blindly analyze the methylation status of SFRP2 and WIF-1 gene promoters in fecal samples from 48 subjects with CRC,35 with adenomas,32 with hyperplastic polyps and 30 endoscopically normal subjects.Additionally,we comparedthe diagnostic efficiency of measuring the hypermethylated SFRP2 and WIF-1 genes in the feces to the fecal occult blood test(FOBT)for the early detection of CRC.RESULTS:Hypermethylated SFRP2 was detected in the feces of 56.3%(27/48)of CRC cases,51.4%(18/35)of adenoma cases and 12.5%(4/32)of patients with hyperplastic polyps.The hypermethylation of WIF-1was detected in 60.4%(29/48),45.7%(16/35)and18.7%(6/32)of fecal samples from CRC,adenoma and hyperplastic polyp patients,respectively.At least one hypermethylated gene was detected in 81.3%(39/48)of CRC and 65.7%(23/35)of adenoma samples.In contrast,only a hypermethylated WIF-1 gene was detected in one case of normal fecal samples.Moreover,no significant associations were observed between SFPR2 and WIF-1 hypermethylation and clinicopathological features.Additionally,81.8%of CRC cases diagnosed as Dukes A stage or advanced adenomas had at least one hypermethylated gene detected,while the detection rate with the FOBT was only 31.8%(P<0.001).CONCLUSION:Hypermethylated SFRP2 and WIF-1genes in fecal DNA are novel and promising molecular biomarkers that have great diagnostic potential for early CRC.

Accuracy of early detection of colorectal tumours by stool methylation markers:A meta-analysis

AIM:To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours.METHODS:Electronic databases including PubMed,Web of Science,Chinese Journals Full-Text Database and Wanfang Journals Full-Text Database were searched to find relevant original articles about methylated genes to be used in diagnosing colorectal tumours. A quality assessment of diagnostic accuracy studies tool(QADAS) was used to evaluate the quality of the included articles,and the Meta-disc 1.4 and SPSS 13.0 software programs were used for data analysis.RESULTS:Thirty-seven articles met the inclusion criteria,and 4484 patients were included. The sensitivity and specificity for the detection of colorectal cancer(CRC) were 73%(95%CI:71%-75%) and 92%(95%CI:90%-93%),respectively. For adenoma,the sensitivity and specificity were 51%(95%CI:47%-54%) and 92%(95%CI:90%-93%),respectively. Pooled diagnostic performance of SFRP2 methylation for CRC provided the following results:the sensitivity was 79%(95%CI:75%-82%),the specificity was 93%(95%CI:90%-96%),the diagnostic OR was 47.57(95%CI:20.08-112.72),the area under the curve was 0.9565. Additionally,the results of accuracy of SFRP2 methylation for detecting colorectal adenomas were as follows:sensitivity was 43%(95%CI:38%-49%),specificity was 94%(95%CI:91%-97%),the diagnostic OR was 11.06(95%CI:5.77-21.18),and the area under the curve was 0.9563.CONCLUSION:Stool-based DNA testing may be useful for noninvasively diagnosing colorectal tumours and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis.